title: Slow inward calcium currents have no obvious role in muscle excitation-contraction coupling.
abstract: It has been proposed that an influx of calcium ions into twitch muscle fibres during an action potential might initiate contraction. However, when external Ca2+ is lowered to 10(-8) M with EGTA, the fibres can produce normal twitches for many minutes. Nevertheless, a clear Ca2+ influx during contraction has been demonstrated, and it has been found that phasic skeletal muscle has an inward calcium current (ICa) which can give rise to calcium spikes. In certain conditions, a reduction in external Ca2+ with 80-90 mM EGTA results in reversible blockade of excitation-contraction (e-c) coupling, leading some authors to suggest that extracellular Ca2+ moved into the myoplasm due to ICa may be involved in the e-c coupling mechanism that triggers contraction. This proposition was further supported by the localization of ICa in the T-system, which circumvented the problem of the delay due to calcium diffusion from the surface membrane. We have now investigated whether ICa has a clear role in initiating or sustaining contractions in twitch muscle fibres. Our approach was to decrease or eliminate ICa with the calcium-blocking agent diltiazem (Herbesser) and to see how the twitch, tetanic and potassium-contracture tensions were affected. We found that ICa could be decreased or cancelled with the calcium-blocking agent, but that the same concentration of the drug potentiated the twitch, tetanus and contractures. We conclude, therefore, that ICa has no role in e-c coupling. A preliminary report of these results has been presented elsewhere.
mesh_terms: D000200:Action Potentials; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology*; D011188:Potassium / Q000502:physiology
chemical_list: D004533:Egtazic Acid; D004110:Diltiazem; D011188:Potassium; D002118:Calcium